Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma

Immune checkpoint inhibitors (ICIs) show limited efficacy in hepatocellular carcinoma (HCC), to which poor intratumoral drug delivery is likely to contribute. This study demonstrates that intravenous co-administration of the tumor-penetrating peptide iRGD with anti-PD-L1 significantly improves antibody distribution and therapeutic response without increasing toxicity in preclinical HCC models. These findings are highly relevant for clinicians and researchers aiming to enhance ICI effectiveness in solid tumors. Given the ongoing clinical evaluation of iRGD, this simple, non-conjugated strategy offers a feasible and rapidly translatable approach to overcome a key limitation of current ICI therapy and improve outcomes for patients with HCC.

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Publication Details

Journal
JHEP Reports
Published
2026-01-09
DOI
https://doi.org/10.1016/j.jhepr.2026.101731
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
0.00

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article

Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma

Oliver Waidmann, Nadja M. Meindl‐Beinker, Fabian Finkelmeier, Dominic Denk et al.
JHEP Reports
Cancer Immunotherapy and Biomarkers
article

Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma

Oliver Waidmann, Nadja M. Meindl‐Beinker, Fabian Finkelmeier, Dominic Denk, Jan Henrik Klug, Bernhard Brüne, Albrecht Piiper, Blerina Aliraj, Lucía Alcober-Boquet, Lena Germann, Carolina De La Torre, Thomas J. Vogl, Andreas Weigert, Stefan Zeuzem
article en

Abstract

Immune checkpoint inhibitors (ICIs) show limited efficacy in hepatocellular carcinoma (HCC), to which poor intratumoral drug delivery is likely to contribute. This study demonstrates that intravenous co-administration of the tumor-penetrating peptide iRGD with anti-PD-L1 significantly improves antibody distribution and therapeutic response without increasing toxicity in preclinical HCC models. These findings are highly relevant for clinicians and researchers aiming to enhance ICI effectiveness in solid tumors. Given the ongoing clinical evaluation of iRGD, this simple, non-conjugated strategy offers a feasible and rapidly translatable approach to overcome a key limitation of current ICI therapy and improve outcomes for patients with HCC.

JHEP ReportsVol. 8(3)
Goethe University Frankfurt (DE), Heidelberg University (DE), University Hospital Heidelberg (DE), Cardiovascular Center Bethanien (DE), University Hospital Frankfurt (DE), University Medical Centre Mannheim (DE), Frankfurt Cancer Institute (DE)
Deutsche Forschungsgemeinschaft, Deutschen Konsortium für Translationale Krebsforschung, National Institutes of Health, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 94%
Cancer Immunotherapy and Biomarkers
DOIOpen Access PDFOpenAlex
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